ArticleBritish journal of cancer2022
FAK promotes stromal PD-L2 expression associated with poor survival in pancreatic cancer.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.Clinical and experimental medicine · 2026Review
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- Exploring the interactions of integrins and CEACAM6 (Review).Experimental and therapeutic medicine · 2025Review
- Review
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Focal adhesion kinase-mediated interaction between tumor and immune cells in the tumor microenvironment: implications for cancer-associated therapies and tumor progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- The integrin adhesome and control of anti-tumour immunity.Biochemical Society transactions · 2024Review
- Persistence of lung structural and functional alterations at one year post-COVID-19 is associated with increased serum PD-L2 levels and altered CD4/CD8 ratio.Immunity, inflammation and disease · 2024Article
- Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer.Gut · 2023Article
- PD-L2 overexpression on tumor-associated macrophages is one of the predictors for better prognosis in lung adenocarcinoma.Medical molecular morphology · 2023Article
- High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast.Frontiers of medicine · 2023Article
- Development and validation of an inflammatory response-related signature in triple negative breast cancer for predicting prognosis and immunotherapy.Frontiers in oncology · 2023Article
- Pan-cancer analysis identifies PD-L2 as a tumor promotor in the tumor microenvironment.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPancreatic Cancer is one of the most lethal cancers, with less than 8% of patients surviving 5 years following diagnosis. The last 40 years have seen only small incremental improvements in treatment options, highlighting the continued need to better define the cellular and molecular pathways contributing to therapy response and patient prognosis.
methodsWe combined CRISPR, shRNA and flow cytometry with mechanistic experiments using a Kras
resultsHere, we identify that expression of the immune checkpoint, Programmed Death Ligand 2 (PD-L2), is associated with poor prognosis, tumour grade, clinical stage and molecular subtype in patients with Pancreatic Ductal Adenocarcinoma (PDAC). We further show that PD-L2 is predominantly expressed in the stroma and, using an orthotopic murine model of PDAC, identify cancer cell-intrinsic Focal Adhesion Kinase (FAK) signalling as a regulator of PD-L2 stromal expression. Mechanistically, we find that FAK regulates interleukin-6, which can act in concert with interleukin-4 secreted by CD4 T-cells to drive elevated expression of PD-L2 on tumour-associated macrophages, dendritic cells and endothelial cells.
conclusionsThese findings identify further complex heterocellular signalling networks contributing to FAK-mediated immune suppression in pancreatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.